Extensive cross-regulation of post-transcriptional regulatory networks in Drosophila
- Marcus H. Stoiber1,2,
- Sara Olson3,
- Gemma E. May3,
- Michael O. Duff3,
- Jan Manent4,
- Robert Obar4,
- K.G. Guruharsha4,5,
- Peter J. Bickel1,
- Spyros Artavanis-Tsakonas4,5,
- James B. Brown2,6,
- Brenton R. Graveley3 and
- Susan E. Celniker2
- 1Department of Biostatistics, University of California Berkeley, Berkeley, California 94720, USA;
- 2Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
- 3Department of Genetics and Genome Sciences, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030, USA;
- 4Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 5Biogen Incorporated, Cambridge, Massachusetts 02142, USA;
- 6Department of Statistics, University of California Berkeley, Berkeley, California 94720, USA
- Corresponding authors: celniker{at}fruitfly.org, graveley{at}uchc.edu, jbbrown{at}lbnl.gov, artavanis{at}hms.harvard.edu
Abstract
In eukaryotic cells, RNAs exist as ribonucleoprotein particles (RNPs). Despite the importance of these complexes in many biological processes, including splicing, polyadenylation, stability, transportation, localization, and translation, their compositions are largely unknown. We affinity-purified 20 distinct RNA-binding proteins (RBPs) from cultured Drosophila melanogaster cells under native conditions and identified both the RNA and protein compositions of these RNP complexes. We identified “high occupancy target” (HOT) RNAs that interact with the majority of the RBPs we surveyed. HOT RNAs encode components of the nonsense-mediated decay and splicing machinery, as well as RNA-binding and translation initiation proteins. The RNP complexes contain proteins and mRNAs involved in RNA binding and post-transcriptional regulation. Genes with the capacity to produce hundreds of mRNA isoforms, ultracomplex genes, interact extensively with heterogeneous nuclear ribonuclear proteins (hnRNPs). Our data are consistent with a model in which subsets of RNPs include mRNA and protein products from the same gene, indicating the widespread existence of auto-regulatory RNPs. From the simultaneous acquisition and integrative analysis of protein and RNA constituents of RNPs, we identify extensive cross-regulatory and hierarchical interactions in post-transcriptional control.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.182675.114.
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Freely available online through the Genome Research Open Access option.
- Received August 7, 2014.
- Accepted June 10, 2015.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
